A Predictive Index for Postoperative Deep Vein Thrombosis in Thoracic Surgery Patients.

In a single-centre prospective trial 200 consecutive patients undergoing thoracic surgery were randomised to receive one of two prophylactic regimes against deep vein thrombosis (DVT). These were 5000 units of subcutaneous heparin twice a day, alone or combined with the wearing of graded compression stockings. The diagnosis of DVT was made clinically and with 131I labelled fibrinogen. Six DVTs developed in the stocking group and 11 in the non-stocking group. The results suggest that the use of stockings reduces the incidence of DVT when added to herparin but the difference is not statistically significant. To obtain a predictive index for the development of DVT, discriminant analysis was applied to the control and stocking groups separately and combined. Five simple clinical variables gave a true positive prediction rate, for the combined group, of 94% and a false positive prediction rate of 26%.

^Computer Centre, Bristol Polytechnic, Bristol. ABSTRACT 'n a single-centre prospective trial 200 consecutive patients undergoing thoracic surgery were randomised to receive one of two prophylactic regimes against deep vein thrombosis (DVT). These were 5000 units of subcutaneous heparin twice a day, alone or combined with the wearing of graded compression stockings. The diagnosis of DVT was made clinically and with 131l labelled fibrinogen. Six DVTs developed in the stocking group and 11 in the non-stocking group. The results suggest that the use of stockings reduces the incidence of DVT When added to heparin but the difference is not statistically significant. To obtain a predictive index for the development of DVT, discriminant analysis was applied to the control and stocking groups separately and combined. Five

PATIENTS AND METHODS
Two hundred consecutive patients, (135 males, 65 females) aged over 18, were randomly allocated to two groups. The control group received low dose subcutaneous heparin alone, while the stocking group received heparin and wore graded compression stockings. All patients received 5000 units of heparin with their pre-medication and 12 hourly thereafter for four days, or until fully mobile if that was longer. The thigh length stockings (TED, Kendall Co.) were fitted the day before operation and worn continuously until the end of the study. All patients underwent routine physiotherapy encouraging gentle exercise while in bed and early ambulation where possible.

Clinical Data
The following clinical data were obtained: age; weight; height; sex; smoking habits; presence of varicose veins and history of venous thromboembolic disease (Pre-VTED). The male patients' desirable weight was calculated using the empirical formula: The females' desirable weight was taken as five kilogrammes less than for males of the same height. Desirable weight calculated by this means compares well with that quoted in Documenta Geigy for persons of medium frame. The desirable weight subtracted from the patient's weight gave amount 'overweight' in kilogrammes. Also recorded were the number of days the patient was confined to bed before and after surgery; as was whether the operation was major or minor, the region (lung or others), and blood loss. Haematological analysis was carried out and included fibrin degradation products, activated partial thromoplasmin time, British comparative ratio, white cell count, haemoglobin, haematocrit and platelet counts.

Diagnosis of DVT
i) 131l-fibrinogen scanning DVT was diagnosed by the 131l-fibrinogen test with 3.7 megabequerel (MBq) given on the day before surgery and if a low count rate made it necessary, another 3.7 MBq was given about one week later. Using the technique of Negus et al 1968, the patients were scanned preoperatively then on alternate days, excluding Sunday, for 14 days or until discharge from hospital if that was sooner. DVT was diagnosed when the counts rose by 20% and was maintained for at least 24 hours. To protect the thyroid gland, doses of 150 mg of potassium iodide were given preoperatively and then daily throughout the course of the study.

ii) Clinical examination
This was based upon individual assessment of pain in the leg, local tenderness, oedema, dilated superficial veins and elevated skin temperation.
iii) Ascending venography This was limited to those cases where there was a definite clinical diagnosis with a negative fibrinogen scan.

Statistical Analysis
The Statistical Package for the Social Sciences or SPSS (Nie et al 1975, Hull andNie 1981) was used to provide frequency distributions, statistical and discriminant analyses for a variety of sub-groups and of the total data. Missing values were omitted from the analysis of that particular variable. Non-significance (n.s.) is taken when p>0.050. During discriminant analysis a list of variables is presented to the computer for possible inclusion in the discriminant equation. A step-wise approach is used whereby a variable is added to the discriminant function on the basis of maximising the distance between the group means. Positive values of the function imply a high risk of DVT, and conversely, negative values a low risk. Compromise between adequate sensitivity and poor specifity is embodied in the constant factor of the equation.

Comparison of control and stocking groups.
There were 100 patients in each of the control and stocking groups and these were well matched for all the clinical and haematological variables investigated.

Incidence of DVT
Of the 200 patients entered in the trial 38 were excluded from the DVT analysis. Of these eleven failed to receive heparin, 16 died before 14 days and 11 had incomplete scanning data. Sixteen patients developed a DVT as diagnosed by 131l-fibrinogen and a seventeenth DVT was included where a patient had a negative 131lfibrinogen scan, clinical evidence of a PE and a positive venogram. Thrombosis developed in 11 of the 78 in the control group (14%) and in 6 of the 84 in the stocking group (7%). This difference in frequency is not statistically significant (x2=1.41, p>0.20).
Considering the 131l-fibrinogen positive cases, the mean interval from surgery to the development of DVT was 5.2 days for the control group and 6.5 days for the stocking group. Seven of the ten patients in the control group and four of the six in the stocking group were receiving heparin when the clot was first detected (figure 1).

Initial analysis
Preoperative variables showing a significant positive association with DVT for all patients were age, pre-VTED and the presence of varicose veins (Tables 1 and 2)-There was a negative association association between the platelet count and DVT. The only operative factor that was significant was operation site which indicated that DVT was less prevalent after operations on the lung. The variables associated with DVT for the control and stocking groups separately are also shown in Tables 1 and 2 Histograms showing the day of onset of DVT for control and stocking groups. Figure 1 Histograms showing the day of onset of DVT for control and stocking groups.   The best discriminant function for the eleven DVTs in jhe control group, gave a 91% true positive and a 35% f3lse positive prediction rate. For the six patients with in the stocking group there was an 83% true positive and a 13% false positive prediction rate. As the number DVTs in these two groups is small and since there was n? significant difference in incidence between the 9roups, we also performed discriminant analysis on both 9roups combined. In this case the index was:- 79c+0.68d+0.77e?2.24 This predicted 16 of the 17 clots (94%) with a false Positive rate of 32 out of 122 (26%). A histogram of the Va'ues of the index for all cases with complete data for the five variables chosen is shown in figure 2. * DISCUSSION 16? 0vera" incidence of DVT in this series was 10% (17 of c i| Patients)-We have not been able to show a statisti-^ ly significant improvement in DVT prophylaxis arising ain?11'16 ^ditional use of graded compression stockings hough the incidence was reduced to 7% compared tn 14% jn t(-,e control group. If this improvement is real tof1 9 'ar9er series of patients must be investigated, a a'of 700 patients would give a 75% chance of arriving a significant' result (Boag et al 1971). ^ ?ur patients, none of whom wore stockings, were a9nosed clinically as having had a PE. In the three who a the diagnosis was confirmed at post mortem ex-^'nation. The fourth patient recovered with treatment.
Three of these patients had negative 131l-fibrinogen scans. Samples of clots from one of them showed a negligible radioactivity. The topping-up of 131l-fibrinogen was designed to overcome this problem which was attributed to the concentration of radiopharmaceutical in the site of any haematoma in the thoracotomy wound. Of the six patients with a previous history of DVT both of those in the control group developed a further DVT whilst only one of the four in the stocking group did so.
Comparison of the clinical and fibrinogen uptake findings showed that in the control group five out of the ten 131l-fibrinogen positive cases were also diagnosed clinically whereas in the stocking group only one of the six cases was diagnosed. With such small numbers this difference is not statistically significant but indicates that wearing stockings may interfere with the clinical diagnosis of DVT.
Initial analysis of the all patient data (Tables 1 and 2) identified significant correlations with DVT for age, history of venous thromboembolic disease, and varicose veins which has been found in previous studies. There was also a negative correlation with the pre-operative platelet count; the reason for this is not clear. The sex of the patient and whether there was benign or malignant disease present were not significant.
The second objective of this study was to find a simple yet effective form of prognostic index. Age over 40 years was found to be more useful than age itself, because of the non-linear relationship between age and the incidence of DVT. Similarly 'overweight' proved to be a better predictor of DVT than the patient's actual weight. Although the sex of the patient was not significantly associated with the occurrence of DVT it was consistently selected by the computer as a useful variable for the discriminant function. It is notable that the sign of the coefficient means that being male produces an increase in the prognostic index implying an increased risk of DVT. Our aim was to derive predictive indices for the control and stocking groups separately but the number of DVTs was too few to do this properly. Correlations of variables with DVT for the separate groups indicate that the index for the combined group is not ideal and that separate indices might be more powerful, but, a larger trial would be necessary to prove this.
The discriminating power of predictive index for the combined group is comparable with that of Clayton et al 1976, but uses simple clinical factors only, making it suitable for a pocket-calculator or computerised patient admission system. ADDENDUM Our policy since this study is now to use subcutaneous Heparin routinely in all patients, and in the high risk (high predictive index) group we use Heparin and graded stockings.